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硫酸化两性离子聚(磺酸甜菜碱甲基丙烯酸酯)水凝胶促进完全皮肤再生。

Sulfated zwitterionic poly(sulfobetaine methacrylate) hydrogels promote complete skin regeneration.

机构信息

School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang 325027, China.

School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang 325027, China; PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou, China.

出版信息

Acta Biomater. 2018 Apr 15;71:293-305. doi: 10.1016/j.actbio.2018.02.034. Epub 2018 Mar 11.

DOI:10.1016/j.actbio.2018.02.034
PMID:29535009
Abstract

UNLABELLED

Skin wound healing is a still long-history challenging problem and impeded by the foreign-body reaction including severe inflammation response, poor neovascularization, incomplete re-epithelialization and defective ECM remodeling. Development of biocompatible polymers, in combination with specific drugs or growth factors, has been considered as a promising strategy to treat skin wounds. Significant research efforts have been made to develop poly(ethylene glycol) PEG-based polymers for wound healing, however less efforts has been paid to zwitterionic materials, some of which have demonstrated their super low-fouling property in vitro and anti-inflammatory property in vivo. Here, we synthesized ultra-low-fouling zwitterionic sulfated poly(sulfobetaine methacrylate) (polySBMA) hydrogels and applied them to full-thickness cutaneous wounds in mice. The healing effects of SBMA hydrogels on the wound closure, re-epithelialization ratio, ECM remodeling, angiogenesis, and macrophage responses during wound healing processes were histologically evaluated by in vivo experiments. Collective results indicate that SBMA hydrogels promote full-thickness excisional acute wound regeneration in mice by enhancing angiogenesis, decreasing inflammation response, and modulating macrophage polarization. Consistently, the incorporation of SBMA into PEG hydrogels also improved the overall wound healing efficiency as compared to pure PEG hydrogels. This work demonstrates zwitterionic SBMA hydrogels as promising wound dressings for treating full-thickness excisional skin wounds.

STATEMENT OF SIGNIFICANCE

Development of highly effective wound regeneration system is practically important for biomedical applications. Here, we synthesized ultra-low-fouling zwitterionic sulfated poly(sulfobetaine methacrylate) (polySBMA) hydrogels and applied it to full-thickness cutaneous wounds in mice, in comparison with PEG hydrogels as a control. We are the first to examine and reveal the difference between zwitterionic SBMA hydrogels and PEG hydrogels using a full-thickness excisional mice model. Overall, a series of in vivo systematic tests demonstrated that zwitterionic SBMA hydrogels exhibited superior wound healing property in almost all aspects as compared to PEG hydrogels.

摘要

未加标签

皮肤伤口愈合是一个长期存在的具有挑战性的问题,其受到异物反应的阻碍,包括严重的炎症反应、新生血管形成不良、不完全的再上皮化和细胞外基质重塑缺陷。开发生物相容性聚合物,并与特定药物或生长因子结合,被认为是治疗皮肤伤口的一种有前途的策略。人们已经做出了重大的研究努力来开发用于伤口愈合的聚乙二醇(PEG)基聚合物,但在两性离子材料方面的研究较少,其中一些材料在体外表现出超低的污染特性,在体内表现出抗炎特性。在这里,我们合成了超低污染的两性离子磺化聚(磺基甜菜碱甲基丙烯酸酯)(polySBMA)水凝胶,并将其应用于小鼠的全层皮肤伤口。通过体内实验,从伤口闭合、再上皮化率、细胞外基质重塑、血管生成和伤口愈合过程中巨噬细胞反应等方面对 SBMA 水凝胶对伤口愈合的影响进行了组织学评估。结果表明,SBMA 水凝胶通过增强血管生成、减少炎症反应和调节巨噬细胞极化,促进了小鼠全层急性伤口的再生。一致地,与纯 PEG 水凝胶相比,将 SBMA 掺入 PEG 水凝胶中也提高了整体伤口愈合效率。这项工作证明了两性离子 SBMA 水凝胶作为治疗全层皮肤切口伤口的有前途的伤口敷料。

意义声明

开发高效的伤口再生系统对于生物医学应用具有重要的实际意义。在这里,我们合成了超低污染的两性离子磺化聚(磺基甜菜碱甲基丙烯酸酯)(polySBMA)水凝胶,并将其应用于小鼠的全层皮肤伤口,与 PEG 水凝胶作为对照。我们是第一个使用全层切除小鼠模型来检查和揭示两性离子 SBMA 水凝胶和 PEG 水凝胶之间差异的。总的来说,一系列体内系统测试表明,与 PEG 水凝胶相比,两性离子 SBMA 水凝胶在几乎所有方面都表现出更好的伤口愈合性能。

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